Multiple Myeloma Drug Therapies

doctor-discussing-myeloma-treatment-drugs
Multiple myeloma drug therapies consist of two types. One type of therapy is to control the myeloma or kill myeloma cells. The other is to alleviate symptoms and manage complications of the disease (such as bone damage) as well as side effects of treatment. This is known as supportive therapy. There are now 5 drug classes for the treatment of multiple myeloma: immunomodulatory drugs, proteasome inhibitors, chemotherapy, histone deacetylase inhibitor (HDAC inhibitor), and steroids.

Monoclonal Antibodies

Darzalex™ (daratumumab)
Darzalex™, also known as daratumumab, is the first monoclonal antibody approved for use in multiple myeloma. Darzalex is made by Janssen Biotech and Genmab.

Empliciti™ (elotumumab)
Empliciti™, also known as elotuzumab, is a monoclonal antibody approved for use in multiple myeloma. Empliciti is made by Bristol-Myers Squibb and AbbVie.

IMiDs (immunomodulatory drugs)

Revlimid® (lenalidomide)
Oral medication that is effective across the spectrum of myeloma disease.

Pomalyst® (pomalidomide)
Newer IMiD that is similar to Revlimid but is more potent. It is FDA approved for use in patients with relapsed/refractory myeloma and is being studied in other types of patients.

Thalomid® (thalidomide)
Older drug shown to be effective across the spectrum of myeloma disease; peripheral neuropathy (nerve problems) is a common side effect and can be irreversible. It is infrequently used in the US.

Proteasome inhibitors

Ninlaro (ixazomib)
The U.S. Food and Drug Administration granted approval for Ninlaro (ixazomib). Ninlaro is the first oral proteasome inhibitor and is approved in combination with Revlimid (lenalidomide) and dexamethasone.

Velcade® (bortezomib)
Medication used across the entire spectrum of myeloma disease. Given as an injection under the skin (subcutaneously) or intravenously. Patients who have the DNA alteration t(4;14) should receive a treatment regimen that includes a proteasome inhibitor.

Kyprolis® (carfilzomib)
Newer proteasome inhibitor given intravenously. It is FDA approved for use in
patients with relapsed/refractory myeloma and is being studied in other types of patients.

Chemotherapy

Doxil® (doxorubicin HCl liposome injection)
Drug given intravenously in patients with relapsed/refractory myeloma, usually in combination with Velcade. Side effects include mouth sores, swelling, blisters on the hands or feet, and possible heart problems. It is less frequently used.

Alkylator chemotherapy
Other types of chemotherapy drugs that have been used for many years to treat myeloma. They may be used in combination with other types of myeloma drugs. Examples are melphalan and cyclophosphamide.

Histone deacetylase inhibitor (HDAC inhibitor)

Farydak® (Panobinostat)
Farydak® is a histone deacetylase inhibitor that is administered in combination with Velcade® (bortezomib) and dexamethasone for patients with relapsed/refractory multiple myeloma. It is administered as an oral medication.

Steroids (corticosteroids)

Dexamethasone (dex) and prednisone
Drugs used for decades to treat myeloma throughout the spectrum of disease; used in combination with other myeloma drugs.

Stem cell transplantation

High-dose chemotherapy and stem cell transplantation.
The use of higher doses of chemotherapy, usually melphalan, followed by transplantation of blood-producing stem cells to replace healthy cells damaged by the chemotherapy.

Options for initial therapy

The choice of a patient’s initial treatment depends on many factors, including the features of the myeloma itself, anticipated risk of side effects, convenience, and the familiarity of the treating physician with the given regimen.

Regimens that are options for patients who are candidates for stem cell transplantation may also be appropriate for patients who are not transplant candidates.

Myeloma treatments consist of either triplets (three drugs) or doublets (two drugs). Generally triplets are preferred. Doublets may also be considered, particularly in cases where the side effects of triplets are a concern. Clinical trials are an option that patients may want to discuss with their doctors.

Triplets include:
■ Revlimid-Velcade-dex (RVD)
Revlimid plus Velcade and dex (RVD) is one of the most commonly used regimens today. Studies have shown that this combination produces a very high response rate among patients with newly diagnosed symptomatic myeloma.

■ Velcade-cyclophosphamide-dex (VCD or CyBorD)
High response rates and rapid responses have been seen in Phase II trials (the second stage of drug studies, designed to test effectiveness).

■ Velcade-Thalomid-dex (VTD)
The combination of Velcade, Thalomid and, dexamethasone has been demonstrated to be highly effective in a Phase III study (the most advanced stage of drug development). Learn more

Doublets (most often used in elderly or frail patients) include:
■ Revlimid-dex (Rd)
The effectiveness of Revlimid-low-dose-dex is well established.

■ Velcade-dex (Vd)
Velcade in combination with dexamethasone as initial therapy was shown to be as effective in patients with whose myeloma has characteristics indicative of more aggressive disease as it was in patients without these characteristics.

Four-drug combinations have also been studied. The challenge with these regimens is the potential for increased side effects, and research is ongoing to determine the balance of effectiveness and tolerability.

Melphalan (MP) based regimens are also options for patients who are not candidates for transplant. These regimens are infrequently used in the US, as there are effective options available with fewer side effects.

You and your doctor will discuss the treatment regimen that is right for you.

Length of therapy for stem cell transplant candidates

Patients who are candidates for transplant may choose to have a transplant after three to four cycles of initial therapy to reduce the amount of myeloma cells (also known as induction therapy) or may decide to continue their initial therapy and potentially consider transplant later in the disease course. Maintenance therapy, which is additional treatment given after initial therapy with the goal of improving long-term outcomes, often follows transplantation.

Length of therapy for non-transplant patients

The length of therapy varies for patients who are not candidates for transplant or who choose not to undergo transplant. While some doctors recommend continuous treatment until there is evidence of myeloma progression, others recommend treatment for a fixed period of time, generally until the response of the disease to the treatment reaches a plateau. The specific characteristics of your myeloma, your preferences, and your doctor’s perspective are considerations in determining the length of therapy. Studies are ongoing to determine the best approach.

Visit the Multiple Myeloma Knowledge Center for more information on multiple myeloma treatments.